title: Horizontally acquired glycosyltransferase operons drive salmonellae lipopolysaccharide diversity.
abstract: The immunodominant lipopolysaccharide is a key antigenic factor for Gram-negative pathogens such as salmonellae where it plays key roles in host adaptation, virulence, immune evasion, and persistence. Variation in the lipopolysaccharide is also the major differentiating factor that is used to classify Salmonella into over 2600 serovars as part of the Kaufmann-White scheme. While lipopolysaccharide diversity is generally associated with sequence variation in the lipopolysaccharide biosynthesis operon, extraneous genetic factors such as those encoded by the glucosyltransferase (gtr) operons provide further structural heterogeneity by adding additional sugars onto the O-antigen component of the lipopolysaccharide. Here we identify and examine the O-antigen modifying glucosyltransferase genes from the genomes of Salmonella enterica and Salmonella bongori serovars. We show that Salmonella generally carries between 1 and 4 gtr operons that we have classified into 10 families on the basis of gtrC sequence with apparent O-antigen modification detected for five of these families. The gtr operons localize to bacteriophage-associated genomic regions and exhibit a dynamic evolutionary history driven by recombination and gene shuffling events leading to new gene combinations. Furthermore, evidence of Dam- and OxyR-dependent phase variation of gtr gene expression was identified within eight gtr families. Thus, as O-antigen modification generates significant intra- and inter-strain phenotypic diversity, gtr-mediated modification is fundamental in assessing Salmonella strain variability. This will inform appropriate vaccine and diagnostic approaches, in addition to contributing to our understanding of host-pathogen interactions.
authors.affiliation: Centre for Immunology and Infection, Hull York Medical School and the Department of Biology, University of York, York, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Davies
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Broadbent
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.forename: Marjan W
authors.initials: MW
authors.lastname: van der Woude
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism; D022761:Gene Transfer, Horizontal / Q000235:genetics*; D014644:Genetic Variation; D016680:Genome, Bacterial; D016695:Glycosyltransferases / Q000235:genetics*; D006090:Gram-Negative Bacteria / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000235:genetics; D019779:Salmonella enterica / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D000942:Antigens, Bacterial; D008070:Lipopolysaccharides; D016695:Glycosyltransferases